1. Field of the Invention
This invention is directed to an estrogenic/progestogenic contraceptive regimen with continuous and/or extended dosing of the estrogenic component. The inventive regimen provides for low daily estrogenic hormone exposure without compromising contraceptive efficacy or cycle control. A contraceptive kit that may be used to practice the method of the invention is also disclosed.
2. Related Background Art
Contraceptive compositions containing both estrogenic and progestogenic compounds are known to be effective in controlling ovulation and conception. The progestogenic component of the composition is primarily responsible for the contraceptive efficacy of the composition, while the estrogenic component is included primarily to reduce undesired side effects, such as breakthrough bleeding or spotting. It is thought that small amounts of estrogen help stabilize the endometrium and allow cyclic withdrawal bleeding, similar to the natural menstrual cycle.
The earliest of these estrogenic/progestogenic contraceptive compositions was administered monophasically (fixed dose) and contained a relatively high level of estrogenic component. U.S. Pat. No. 4,921,843 relates to the administration of an estrogen-only component from day 2 to day 7 of the menstrual cycle, followed by administration of a combination of estrogen and progestin from day 7 to day 28 of the menstrual cycle. U.S. Pat. No. 5,280,023 and U.S. Pat. No. 5,510,341 describe the administration of an estrogen-only component for 5 to 14 days at the beginning of the cycle, followed by 23 to 14 days of an estrogen/gestagen combination. U.S. Pat. No. 5,756,490 discloses combination preparations with 23 or 24 daily units of an estrogen and gestagen, and 4 to 10 daily units of estrogen only. Similarly, U.S. Pat. No. 6,027,749 discloses an estrogen-only component administered for 5, 6, or 7 days. U.S. Pat. No. 5,552,394 discloses administration of tablets that contain both estrogen and progestin for 24 days followed by 4 days of placebo.
U.S. Pat. No. 4,962,098 is directed to a multiphasic contraceptive regimen and describes a triphasic method of contraception using a progestin/estrogen combination in which the amount of estrogen is increased stepwise over the three phases wherein the first phase is 4-7 days, the second phase is 5-8 days and the third phase is 7-12 days. Preferably, administration of the contraceptive compositions for the three phases combined will be 21 days followed by a 7 day placebo period. For all three phases, the progestin is 0.5 to 1.5 mg of norethindrone acetate, while about 10 to 30 mcg of ethinyl estradiol is used in the first phase, about 20 to 40 mcg of ethinyl estradiol is used in the second phase and 30 to 50 mcg of ethinyl estradiol is employed in the third phase.
U.S. Pat. No. 5,747,480 also discloses a multiphasic regimen wherein the progestin component is levonorgestrel. U.S. Pat. No. 5,888,543 discloses various regimens wherein a combination of progestin and estrogen are administered in a monophasic or multiphasic regimen (varied dose, e.g., biphasic or triphasic). In one embodiment, a combination of a progestin composition and an estrogen composition is administered such that the daily dosage of the second phase progestin is greater than the daily dosage of progestin in the first phase and the daily dosage of the second phase estrogen is greater than or equal to the daily dosage of estrogen in the first phase. U.S. Pat. No. 6,479,475 describes multiphasic regimens with 23-25 consecutive days of hormone administration, followed by a 3-5 day hormone-free interval.
U.S. Pat. No. 5,898,032 discloses an extended oral contraceptive regimen wherein estrogen and progestin are administered in a combined dosage form, preferably monophasically, for 60 to 110 consecutive days, followed by an administration free period of 3 to 10 days. The amount of estrogen and progestin administered daily are equivalent to about 5-35 mcg of ethinyl estradiol and about 0.025 to 10 mg of norethindrone acetate, respectively. In one particular embodiment, the combined dosage form is administered for 84 days followed by 7 pill free days. Following this particular regimen is said to result in four treatments and menstrual cycles during the year. However, extended oral contraceptive regimens tend to suffer from poor initial cycle control. Another disadvantage is that once breakthrough bleeding is under control, the user becomes functionally amenorrheic. This does not reassure the user that she is not pregnant.
One constant goal in the oral contraceptive art has been to reduce the hormone levels of such compositions without reducing contraceptive efficacy and increasing undesired side effects. Since the risk is acute thrombosis (as opposed to atherosclerosis), minimizing daily exposure of estrogen is a therapeutic goal. However, as estrogen doses decreased, the incidences of unwanted breakthrough bleeding or spotting have generally increased. Therefore, there remains a need for an oral contraceptive regimen that maintains contraceptive efficacy and provides adequate cycle control with a low daily dose of the estrogenic component.